We have identified the degree of virulence of endogenous eco- as well as xenotropic MuLV as a major determinant in disease incidence in several high and low leukemic strains of mice. Ecotropic virus from the low leukemic strains C3H and BALB/c was replication deficient, XC negative. This virus has multiple defects which affect both precursor processing of the gene product as well as transcriptional control. Selection for rapid replication in fibroblast cells and stimulation of growth in soft agar yield rapidly leukemogenic isolates as well as solid tumor-inducing variants. The rapid leukemia inducing viruses were either eco- or dual tropic. Dual tropism was acquired as a consequence of recombination with either endogenous amphotropic or xenotropic envelope genes. The rapidly leukemogenic isolates share a common gp70 specificity, the MCF antigen. Some of them also have an altered gag gene containing p12 with Mol-specificity. The new mouse sarcoma viruses induce undifferentiated sarcomas in newborn NIH Swiss mice. Their sarc genes differ from both Kirsten as well as Moloney sarcoma virus.